The major goal of this grant proposal is the elucidation of the metabolism and biologic actions of vitamin D and its metabolites. The availability of purified radioactive metabolites of high specific activity will permit detailed studies of the metabolism of 24,25(OH)2D3 and 1,24,25(OH)3D3 in a variety of animal models and experimental conditions. Carefully designed tritiated or non-radioactive chemical analogues of vitamin D metabolites, synthesized in our laboratory, will enable definition of structural determinants for the metabolism, blood transport, tissue and subcellular localization and biologic activity of vitamin D compounds and will direct the synthesis of additional analogues with potential specificity for one or another biologic effect.